Acute pancreatitis is the most common serious complication of endoscopic retrograde cholangiopancreatography (ERCP) and occurs with an incidence between 5 and 15%. Approximately 55% of these occurrences are moderate to severe in magnitude, representing an enormous burden of morbidity, mortality and malpractice claims. The mechanisms of post- ERCP pancreatitis are multifactorial and involve activation of local neural arc pathways, pancreatic enzymes, and the inflammatory cascade. Lidocaine, a commonly used and inexpensive anesthetic and antiarrhythmic, has an inhibitory effect on these neural arc pathways as well as on phospholipase A2, and has been shown to attenuate or prevent acute pancreatitis in animal models. Although it has been suggested, to date there have been no studies performed using intraductal lidocaine for the specific indication of preventing post-ERCP pancreatitis in humans. We hypothesize that lidocaine, when added to the contrast material and infused into the pancreatic duct at the time of ERCP, can reduce the incidence of ERCP-induced pancreatitis by inhibiting local neural reflex arcs and phospholipase A2, both of which are activated by manipulation and inflammation of the pancreatic duct. The goal of this project is to launch a randomized, double-blind, controlled trial of patients referred to Penn State Hershey Medical Center for ERCP with a goal of 570 patients in each arm for a study power of 80%. Patients will be randomized in a 1:1 ratio to control or study group. The control arm will receive contrast dye diluted to 50% with normal saline (standard of care) and the study arm will have contrast dye diluted to 50% with lidocaine (100mg). The primary outcome will be the incidence of acute pancreatitis, defined clinically and biochemically, within 24 hours post procedure with a secondary outcome of serum amylase levels 2 hours post procedure. A safety trial of 10 patients has recently been completed without complication or incident pancreatitis. The results of this study will elucidate if lidocaine is useful in preventing pancreatitis and may shed additional light onto its mechanisms. PUBLIC HEALTH RELEVANCE: Pancreatitis is the most common serious complication of endoscopic retrograde pancreato- cholangiography (ERCP), occurring in 5-15% of patients, with 55% of these cases being considered moderate to severe in magnitude. The goal of this study is to determine if lidocaine is effective in diminishing the risk of post-ERCP pancreatitis, and to further the understanding of the safety and usefulness of lidocaine when used in ERCP.